Pegylated Liposomal Doxobubicin (PLD) Can Be Escalated in a Dose-Dense, 14 Day CDOP-Rituximab Regimen without Affecting Relative Dose Intensity (RDI) in Patients with Diffuse Large B Cell Lymphoma (DLBCL) Who Are Elderly or Have Compromised Cardiac Status.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2692-2692
Author(s):  
Stephen J Noga ◽  
Judy Bosley ◽  
Pamela Nickoles ◽  
Pallavi Kumar ◽  
Erica Monfred
Keyword(s):  
Cardiac Function ◽  
Dose Intensity ◽  
B Cell Lymphoma ◽  
The Elderly ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Poor Performance Status ◽  
Term Survival ◽  
Full Dose ◽  
Dose Dense

Abstract Abstract 2692 Poster Board II-668 Anthracycline/rituximab based chemotherapy such as CHOP-R has become the standard of care for DLBCL where cure is the primary goal. There is a direct correlation between long term survival and the delivery of on time, full dose chemotherapy. Several studies in DLBCL now indicate that this concept of dose intensity may be further exploited by compacting therapy cycles from the usual 21 days to the 14 day “dose dense” regimens. It is hoped that this will result in higher cure rates. Community oncologists often face tough decisions when deciding how to treat the increasing numbers of DLBCL patients who are elderly and have multiple co-morbidities including declining cardiac function and poor performance status (PS). Since PLD has a reported lower cardiac toxicity profile even at higher overall doses than doxorubicin, it was substituted into a dose-dense CHOP-R regimen. Patients >60 years or with left ventricular ejection fractions (LVEF) <45% were enrolled in a phase II dose escalation study of PLD (Doxil*®,20 mg/m2: cohort I, 25 mg/m2: cohort II, 30 mg/m2: cohort III), cyclophosphamide (CY, 750 mg/m2), vincristine (1.4 mg/m2: 2 mg max), prednisone (100 mg PO days 1-5), rituximab (375 mg/m2) on day 1 followed by pegfilgrastim (6 mg, SC) on day 2 of a 14 day cycle. Patients received a planned 6 cycles of chemotherapy or 2 cycles past best response. Safety and SAE's were assessed with each cohort or every 6 patients. Quantitative LVEF was obtained with each cycle, CT's every 3 cycles and PET/CT at baseline and within 60 days of chemotherapy completion. Median age was 76 (62-87) years, 59% were female with baseline LVEF from 12% (with AICD but ECOG PS1) to 75% (PS3). There was no diminution in LVEF for patients receiving >1 cycle of chemotherapy. AE's >grade 2 were neutropenia/fever (n=3), neutropenia (n=1), thrombocytopenia (n=1), chest pain (n=1), hyperglycemia (n=2), CHF (n=1) and worsening pleural effusion (n=1). PPE related to PLD was manageable and minimally delayed therapy. . Patients who were hospitalized (PS >2) or who's PS declined rapidly between study entry and cycle 1 initiation rapidly became too moribund to complete planned therapy. Escalation of the PLD dose from 20 mg/m2 to 30 mg/m2 did not alter the ability to deliver on time, full dose chemotherapy. Decreasing cycle length to 2 weeks actually increased the RDI to 150% over the standard 3 week regimen. This may be beneficial in the elderly where it is still uncertain if lower survival is due to substandard treatment regimens or a more chemo-resistant NHL phenotype. In the first 12 evaluable patients completing full course chemotherapy, 10 patients were in CR (CR +nCR), and 1 in PR within 60 days of chemotherapy completion. At 1 year, 6 patients were in CR and 2 had progressive disease. We conclude that CDOP-R 14 warrants further study in the elderly population and in those DLBCL patients with compromised cardiac function. Disclosures: Noga: Tibotec, Inc: Honoraria, Research Funding, Speakers Bureau; Amgen, Inc: Honoraria, Speakers Bureau. Off Label Use: Doxil. Substitutes for the standard anthracycline, doxorubicin, in the CHOP regimen for agressive NHL.

Can a Dose-Dense RCHOP-Like Regimen Be Effectively Used In a Community Setting? Results of a Phase II Study Employing Pegylated Liposomal Doxorubicin In Elderly (> age 60) or Cardiac Compromised (LVEF <45%) Patients with Diffuse Large B Cell Lymphoma (DLBCL).

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2797-2797
Author(s):  
Stephen J. Noga ◽  
Judith Bosley ◽  
Pamela Nickoles
Keyword(s):  
Phase Ii ◽  
Survival Data ◽  
Research Funding ◽  
Liposomal Doxorubicin ◽  
Pegylated Liposomal Doxorubicin ◽  
Dose Intensity ◽  
B Cell Lymphoma ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Dose Dense

Abstract Abstract 2797 Chemotherapy employing the RCHOP every 21 day regimen has become the standard of care for patients with DLBCL. Although the GELA study did include older patients, NHL incidence rises more steeply with age, with a third of cases occurring in patients over 75 years of age. Community oncologists see an ever-increasing NHL age group with multiple co-morbidities. There is also debate whether DLBCL is more aggressive/chemo-resistant at the higher age range. For many, cardiac issues exclude them from an adriamycin-based regimen and possible cure. Since pegylated liposomal doxorubicin (PLD) has a reported lower cardiac toxicity profile even at higher overall doses than doxorubicin, it was substituted into a dose-dense RCHOP regimen. To this end, we developed a phase II dose-dense/dose escalation study of PLD (Doxil®,20 mg/m2: cohort I, 25 mg/m2: cohort II, 30 mg/m2: cohort III), cyclophosphamide (CY, 750 mg/m2), vincristine (1.4 mg/m2: 2 mg max), prednisone (100 mg PO days 1–5) and rituximab (375 mg/m2) on day 1 followed by pegfilgrastim (Neulasta®, 6 mg, SC) on day 2 of a 14 day cycle. Patients received a planned 6 cycles of chemotherapy or 2 cycles past best response. Patients >60 years or with left ventricular ejection fractions (LVEF) <45% were enrolled with ECOG performance status (PS) of 0 – 3. Three, 6 and 8 patients (17 total) were enrolled on cohorts I – III, respectively, Intent to treat (ITT) data included all patients. Response/survival data excluded 2 patients who deteriorated by start of cycle 1 chemotherapy. Safety and SAE's were assessed with each cohort. Quantitative LVEF was obtained with each cycle, CT's every 3 cycles and PET/CT at baseline and within 60 days of chemotherapy completion. Median age was 78 (62-87), 59% were female and baseline LVEF from 12% (with AICD but ECOG PS1) to 87% (median 60%). There was no reduction in LVEF for patients receiving >1 cycle of chemotherapy. Patients who were hospitalized (PS>2) or who's PS declined rapidly between study entry and cycle 1 initiation rapidly became too moribund to complete planned therapy. Relative dose intensity [RDI: (delivered chemotherapy/time to complete)/(planned chemotherapy/planned time to complete)] for the entire group averaged 96 (83 – 100)% for PLD, median 100%, and 97 (86 – 100)%, median 100%, for cyclophosphamide. Nearly all patients (92%) achieved a CR/nCR with a 77% CR rate. Despite an every 14 day anthracycline regimen, Grade >2 hematologic toxicities were manageable and others were low. Overall Survival in the ITT population was 65% and 37% at 12 and 24 months, respectively. Censoring for patients removed in or after cycle 1 yielded a survival rate of 73% at 12 months and 42% at 24 months. This elderly patient population had significant long term morbidities, post-chemotherapy, leading to mortality from cardiac disease, ARF and liver failure besides lymphoma related causes. Adjusting for the non-lymphoma deaths gave adjusted survivals of 85% and 71% at 12 and 24 months, respectively. We conclude that it is feasible to deliver a dose-dense anthracycline regimen to geriatric patients with acceptable toxicity. Indeed, 71% of study patients were ≥ 70 years and 47% were ≥ 80 years. Microarray analysis may pinpoint which elderly patients may require a more intensive regimen to effect cure. Grade (%) N F/N Hosp F/N Tpenia PPE Cardiac Stomatitis All 88 24 24 82 65 24 47 3 24 12 12 24 6 12 6 4 41 12 12 6 6 - - Neutropenia =N, Febrile Neutropenia =F/N, Hospitalization for F/N = Hosp F/N, Thrombocytopenia = Tpenia, Palmar- Plantar erythrodysesthesia = PPE Disclosures: Noga: Amgen: Honoraria, Research Funding, Speakers Bureau, none; Millenium Takada: Consultancy, Honoraria, Research Funding, Speakers Bureau, none; Ortho-Centicor: Research Funding, Speakers Bureau, none; Cephalon: Honoraria, Speakers Bureau, none; Pfizer: Speakers Bureau, none; Cellgene: Honoraria, Research Funding, Speakers Bureau, none. Off Label Use: Doxil (pegylated liposomal doxorubicin) in place of adriamycin in a CHOP-R regimen for DLBCL.

Tolerability of 2-Weekly CHOP+Rituximab Followed by Yttrium-90 Ibritumomab Tiuxetan (Zevalin) In Patients with Previously Untreated Diffuse Large B Cell Lymphoma (DLBCL): Final Analysis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4918-4918 ◽  
Author(s):  
Andrew Manson ◽  
Reem Karmali ◽  
Irene Dehghan-Paz ◽  
Eduardo Braun ◽  
Teresa O'Brien ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Research Funding ◽  
B Cell Lymphoma ◽  
Left Ventricular ◽  
Neutropenic Fever ◽  
Left Ventricular Ejection ◽  
Organizing Pneumonia ◽  
Off Label ◽  
Grade 3 ◽  
Dose Dense

Abstract Abstract 4918 Background: Improved outcomes have been demonstrated in DLBCL with dose dense CHOP (CHOP-14), the addition of immunotherapy to CHOP, and radioimmunotherapy consolidation following CHOP chemotherapy. A prospective, single-arm, open-label, nonrandomized phase II trial was conducted using a combination of the above with dose dense CHOP+R, every 2 weeks, followed by radioimmunotherapy consolidation to evaluate its efficacy and safety in untreated DLBCL patients. Patients and Methods: 20 eligible patients (measurable disease, age >18 years, performance status 0–2, adequate marrow, liver and kidney function) with previously untreated DLBCL were enrolled. Patients with transformed lymphoma were excluded. Patients received standard CHOP along with rituximab 375mg/m2 IV on day 1, every two weeks for 6 cycles, followed by Zevalin 6–8 weeks later. Efficacy of Study: In 20 treated patients, ORR was 100% with 90% CR and 10% PR. 16 patients received the entire treatment regimen as intended. 3 patients (15%) relapsed. All relapses were retreated with one patient now in CR and 2 deceased. One other patient, who did not receive Zevalin, is also deceased from organizing pneumonia 2 years after last chemotherapy. Safety Results: The most common adverse effects of this regimen were hematological. All patients (n=20) had anemia during CHOP+R pre-Zevalin, 15 (75%) patients with grade 1/2 and 5 (25%) with grade 3 anemia. 11 patients had thrombocytopenia, 4 with grade 3/4 toxicity. Neutropenia was present during CHOP+R therapy in 14 patients (70%), 2 cases of grade 2 and 12 cases of grade 4 toxicity. However, neutropenic fever only occurred in 4 patients, all with grade 1/2 neutropenia. Neuropathy was also a common toxicity (15 patients), with grade 3 toxicity occurring in 4 patients. Less common adverse effects, all ≤ grade 2, included anorexia, constipation, nephrolithiasis, diarrhea, urinary frequency, dysgeusia and rhinitis. With completion of dose dense chemotherapy, one patient had organizing pneumonia, one had grade 2 pneumonitis, and one had bronchiectasis, all precluding the use of Zevalin. Pre and post chemotherapy MUGA scans demonstrated stable left ventricular ejection fractions in all but one patient, who remains in CR. Zevalin was completed by 16 patients (80%). Zevalin induced grade 3/4 cytopenias occurred in 8 patients (50%), the most common being neutropenia (all 8 patients) with no cases of neutropenic fever. 12 (75%) patients experienced thrombocytopenia, though only 2 had grade 3/4 effects. Grade 3 syncope occurred in one patient. All other non-hematologic effects were ≤ grade 2 and included neuropathy, sinus and yeast infections, folliculitis, rash, diarrhea, nausea, and urinary incontinence. Conclusion: Consolidation with Zevalin radioimmunotherapy following dose dense CHOP+R therapy is well tolerated, safe and non-life threatening among our sample population of untreated DLBCL. Disclosures: Off Label Use: Chemotherapy with R-CHOP every 21 days is the standard of care for DLBCL in the front-line setting. We are administering R-CHOP every 14 days for dose intensification followed by zevalin (radioimmunotherapy) consolidation for untreated DLBCL. This regimen is off-label. Gregory: Amgen: Consultancy; Astellas: Research Funding; Celgene: Research Funding; Cephalon: Research Funding, Speakers Bureau; Genentech (Roche): Consultancy, Research Funding, Speakers Bureau; Glaxo-Smith-Kline: Research Funding; Immunomedics: Research Funding; NCIC CTG: Research Funding; Novartis: Consultancy, Research Funding; Onyx (Proteolix): Research Funding; Spectrum Pharmaceuticals: Consultancy.

Heart Failure with Preserved Ejection Fraction – A Review

2012 ◽  
Vol 9 (1) ◽  
pp. 90-95 ◽  
Author(s):  
Otto A Smiseth ◽  
Anders Opdahl ◽  
Espen Boe ◽  
Helge Skulstad
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Heart Failure ◽  
The Elderly ◽  
Left Ventricular ◽  
Filling Pressure ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Reduced Ejection Fraction ◽  
Objective Evidence

Heart failure with preserved left ventricular ejection fraction (HF-PEF), sometimes named diastolic heart failure, is a common condition most frequently seen in the elderly and is associated with arterial hypertension and left ventricular (LV) hypertrophy. Symptoms are attributed to a stiff left ventricle with compensatory elevation of filling pressure and reduced ability to increase stroke volume by the Frank-Starling mechanism. LV interaction with stiff arteries aggravates these problems. Prognosis is almost as severe as for heart failure with reduced ejection fraction (HF-REF), in part reflecting co-morbidities. Before the diagnosis of HF-PEF is made, non-cardiac etiologies must be excluded. Due to the non-specific nature of heart failure symptoms, it is essential to search for objective evidence of diastolic dysfunction which, in the absence of invasive data, is done by echocardiography and demonstration of signs of elevated LV filling pressure, impaired LV relaxation, or increased LV diastolic stiffness. Antihypertensive treatment can effectively prevent HF-PEF. Treatment of HF-PEF is symptomatic, with similar drugs as in HF-REF.

scholarly journals A Randomized Controlled Trial to Study the Effect of Yoga Therapy on Cardiac Function and N Terminal Pro BNP in Heart Failure

2014 ◽  
Vol 9 ◽  
pp. IMI.S13939 ◽  
Author(s):  
Bandi Hari Krishna ◽  
Pravati Pal ◽  
G. K. Pal ◽  
J. Balachander ◽  
E. Jayasettiaseelon ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Medical Therapy ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Tei Index ◽  
Ventricular Ejection Fraction ◽  
Yoga Therapy ◽  
Standard Medical Therapy

Aims The purpose of this study was to evaluate whether yoga training in addition to standard medical therapy can improve cardiac function and reduce N terminal pro B-type natriuretic peptide (NT pro BNP) in heart failure (HF). Methods 130 patients were recruited and randomized into two groups: Control Group (CG) ( n = 65), Yoga Group (YG). In YG, 44 patients and in CG, 48 patients completed the study. Cardiac function using left ventricular ejection fraction (LVEF), myocardial performance index (Tei index), and NT pro BNP, a biomarker of HF, was assessed at baseline and after 12 weeks. Result Improvement in LVEF, Tei index, and NT pro BNP were statistically significant in both the groups. Furthermore, when the changes in before and after 12 weeks were in percentage, LVEF increased 36.88% in the YG and 16.9% in the CG, Tei index was reduced 27.87% in the YG and 2.79% in the CG, NT pro BNP was reduced 63.75% in the YG and 10.77% in the CG. The between group comparisons from pre to post 12 weeks were significant for YG improvements (LVEF, P < 0.01, Tei index, P < 0.01, NT pro BNP, P < 0.01). Conclusion These results indicate that the addition of yoga therapy to standard medical therapy for HF patients has a markedly better effect on cardiac function and reduced myocardial stress measured using NT pro BNP in patients with stable HF.

HDL Cholesterol Level Predicts Survival in Men After Coronary Artery Bypass Graft Surgery

Circulation ◽  
2000 ◽  
Vol 102 (suppl_3) ◽  
Author(s):  
JoAnne Micale Foody ◽  
Francis D. Ferdinand ◽  
Gregory L. Pearce ◽  
Bruce W. Lytle ◽  
Delos M. Cosgrove ◽  
...  
Keyword(s):  
Artery Bypass ◽  
Bypass Graft ◽  
Hdl Cholesterol ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Term Survival ◽  
Ventricular Ejection Fraction ◽  
Low Hdl ◽  
History Of ◽  
Extent Of Disease

Background —HDL cholesterol (HDL-C) is an important independent predictor of atherosclerosis, yet the role that HDL-C may play in the prediction of long-term survival after CABG remains unclear. The risk associated with a low HDL-C level in post-CABG men has not been delineated in relation to traditional surgical variables such as the use of arterial conduits, left ventricular function, and extent of disease. Methods and Results —We performed a prospective, observational study of 432 men who underwent CABG between 1978 and 1979 in whom preoperative HDL-C values were available. Baseline lipid and lipoprotein values, history of diabetes mellitus and hypertension, left ventricular ejection fraction, extent of disease, and use of internal thoracic arteries were recorded. Hazard ratios (HRs) were determined in the patients with and without a low HDL-C level, which was defined as the lowest HDL-C quartile (HDL-C ≤35 mg/dL). After adjustment for age, as well as for baseline metabolic parameters and surgical variables just noted, HDL-C corresponded to both overall (HR 0.40, CI 0.20 to 0.83, P =0.01) and event-free (HR 0.41, CI 0.24 to 0.70, P =0.001) survival. Patients with a high HDL-C level (>35 mg/dL) were 50% more likely to survive at 15 years than were patients with low HDL-C level (≤35 mg/dL) (74% versus 57% adjusted survival, respectively; HR 1.72, P =0.005). In addition, HDL-C showed a strong effect on time-to-event survival such that patients with an HDL-C level of >35 mg/dL were 50% more likely to survive without a subsequent myocardial infarction or revascularization (HR 1.42, P =0.02). Conclusions —HDL-C is an important predictor of survival in post-CABG patients. In this study of >8500 patient-years of follow-up, HDL-C was the most important metabolic predictor of post-CABG survival. One third fewer patients survive at 15 years if their HDL-C levels are ≤35 mg/dL at the time of CABG. The measurement of HDL-C provides a compelling strategy for the identification of high-risk subsets of patients who undergo CABG.

Abstract 1213: Cardiac Overexpression of Epac1 in Transgenic Mice Protects Heart from Lipopolysaccharide-induced Cardiac Dysfunction and Inhibits JAK-STAT Pathway

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Satoshi Okumura ◽  
Yunzhe Bai ◽  
Meihua Jin ◽  
Sayaka Suzuki ◽  
Akiko Kuwae ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cyclic Amp ◽  
Transgenic Mice ◽  
Cardiac Function ◽  
Proinflammatory Cytokines ◽  
Cardiac Dysfunction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Stat Pathway

The sympathetic nervous system and proinflammatory cytokines are believed to play independent roles in the pathophysiology of heart failure. However, the recent identification of Epac (exchange protein activated by cyclic AMP), a new cyclic AMP-binding protein that directly activates Rap1, have implicated that there may be a potential cross talk between the sympathetic and cytokine signals. In order to examine the role of Epac in cytokine signal to regulate cardiac function, we have generated transgenic mice expressing the human Epac1 gene under the control of alpha-cardiac myosin heavy chain promoter (Epac1-TG), and examined their response in lipopolysaccharide (LPS)-induced cardiac dysfunction, a well established model for sepsis-induced cardiac dysfunction. Sepsis-induced cardiac dysfunction results from the production of proinflammatory cytokines. At baseline, left ventricular ejection fraction (LVEF) was similar (TG vs. NTG, 67±1.7 vs. 69±2.1%, n =7–9). The degree of cardiac hypertrophy (LV(mg)/tibia(mm)) was also similar at 3 months old (TG vs. NTG 4.0±0.1 vs. 4.2±0.1, n =5–6), but it became slightly but significantly greater in Epac1-TG at 5 month old (TG vs. NTG 4.9±0.1 vs. 4.4±0.1, p< 0.05, n =5–7). LPS (5mg/kg) elicited a significant and robust reduction of LVEF in both Epac1-TG and NTG, but the magnitude of this decrease was much less in Epac1-TG at 6 hr after injection (TG vs. NTG 48±2.4 vs. 57±1.8%, p< 0.01, n =6–9). At 24 hr after injection, cardiac function was restored to the baseline in both Epac1-TG and NTG. We also examined the activation of JAK-STAT pathway at 24 hr after injection. The tyrosine phosphorylation of STAT1 (Tyr701) and STAT3 (Tyr705) in LV, which is an indicator of STAT activation, was reduced to a greater degree in Epac1-TG by 31±8.8% ( p< 0.05, n =4) and 29±5.9% ( p< 0.05, n =7), respectively, relative to that in NTG. Taken together, Epac1 protects the heart from the cytokine-induced cardiac dysfunction, at least in part, through the inhibition of the JAK-STAT pathway, suggesting the beneficial role played by sympathetic signal to antagonize proinflammatory cytokine signal in heart failure.

scholarly journals Impact of residence altitude on readmission in patients with heart failure

Open Heart ◽  
2018 ◽  
Vol 5 (2) ◽  
pp. e000865
Author(s):  
Makoto Saito ◽  
Manami Yamaoka ◽  
Mayuri Ohzawa ◽  
Emi Tominaga ◽  
Kayo Takahashi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Winter Season ◽  
The Elderly ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Administrative District ◽  
Ventricular Ejection Fraction ◽  
Using Data ◽  
Lower Temperature ◽  
A Minor

ObjectiveMountain districts normally have tougher geographic conditions than plain districts, which might worsen heart failure (HF) conditions in patients. Also, those places frequently are associated with social problems of ageing, underpopulation and fewer medical services, which might cause delay in detection of disease progression and require more admissions. We investigated the association of residence altitude with readmission in patients with HF.MethodsWe followed 452 patients with HF to determine all-cause readmissions over a median of 1.1 years. The altitude of patient residences, population, proportion of the elderly and number of hospitals or clinics in a minor administrative district (Cho-Aza district) located at the residences were examined using data from the 2010 census and Google Maps.ResultsAll-cause readmissions were observed in 269 (60%) patients. The altitude of ≥200  m was significantly associated with readmissions (HR, 1.49; 95 % CI 1.12 to 1.96; p=0.006) after adjustment for physical and haemodynamic parameters, left ventricular ejection fraction, brain natriuretic peptide and components of the established score for predicting readmission for HF. Altitude was significantly associated with ageing, underpopulation, fewer hospitals or clinics and lower temperature (all p<0.01), with an increased tendency for readmission during the winter season; however, it was not associated with patient clinical parameters.ConclusionsHigh altitude residence may be an important predictor for readmission in patients with HF. This relationship may be confounded by unfavourable sociogeographic conditions at higher altitudes.

scholarly journals β-Hydroxybutyrate Exacerbates Hypoxic Injury by Inhibiting HIF-1α-Dependent Glycolysis in Cardiomyocytes—Adding Fuel to the Fire?

2021 ◽  
Author(s):  
Xiurui Ma ◽  
Zhen Dong ◽  
Jingyi Liu ◽  
Leilei Ma ◽  
Xiaolei Sun ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Ketone Body ◽  
Human Peripheral Blood ◽  
Left Ventricular ◽  
Cell Counting ◽  
Left Ventricular Ejection ◽  
Chow Diet ◽  
Dead Cell ◽  
Hypoxic Conditions

Abstract Purpose Ketone body oxidation yields more ATP per mole of consumed oxygen than glucose. However, whether an increased ketone body supply in hypoxic cardiomyocytes and ischemic hearts is protective or not remains elusive. The goal of this study is to determine the effect of β-hydroxybutyrate (β-OHB), the main constituent of ketone bodies, on cardiomyocytes under hypoxic conditions and the effects of ketogenic diet (KD) on cardiac function in a myocardial infarction (MI) mouse model. Methods Human peripheral blood collected from patients with acute myocardial infarction and healthy volunteers was used to detect the level of β-OHB. N-terminal proB-type natriuretic peptide (NT-proBNP) levels and left ventricular ejection fractions (LVEFs) were measured to study the relationship between plasma β-OHB and cardiac function. Adult mouse cardiomyocytes and MI mouse models fed a KD were used to research the effect of β-OHB on cardiac damage. qPCR, western blot analysis, and immunofluorescence were used to detect the interaction between β-OHB and glycolysis. Live/dead cell staining and imaging, lactate dehydrogenase, Cell Counting Kit-8 assays, echocardiography, and 2,3,5-triphenyltetrazolium chloride staining were performed to evaluate the cardiomyocyte death, cardiac function, and infarct sizes. Results β-OHB level was significantly higher in acute MI patients and MI mice. Treatment with β-OHB exacerbated cardiomyocyte death and decreased glucose absorption and glycolysis under hypoxic conditions. These effects were partially ameliorated by inhibiting hypoxia-inducible factor 1α (HIF-1α) degradation via roxadustat administration in hypoxia-stimulated cardiomyocytes. Furthermore, β-OHB metabolisms were obscured in cardiomyocytes under hypoxic conditions. Additionally, MI mice fed a KD exhibited exacerbated cardiac dysfunction compared with control chow diet (CD)-fed MI mice. Conclusion Elevated β-OHB levels may be maladaptive to the heart under hypoxic/ischemic conditions. Administration of roxadustat can partially reverse these harmful effects by stabilizing HIF-1α and inducing a metabolic shift toward glycolysis for energy production.

scholarly journals Effects of Exercise on Cardiac Function Outcomes in Women Receiving Anthracycline or Trastuzumab Treatment for Breast Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 (18) ◽  
pp. 8336
Author(s):  
Pedro Antunes ◽  
Dulce Esteves ◽  
Célia Nunes ◽  
Anabela Amarelo ◽  
José Fonseca-Moutinho ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Cardiac Function ◽  
Meta Analysis ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Cochrane Library ◽  
Circulating Biomarkers ◽  
Ventricular Ejection Fraction ◽  
Secondary Outcomes

Background: we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of exercise training on cardiac function and circulating biomarkers outcomes among women with breast cancer (BC) receiving anthracycline or trastuzumab-containing therapy. Methods: PubMed, EMBASE, Cochrane Library, Web of Science and Scopus were searched. The primary outcome was change on left ventricular ejection fraction (LVEF). Secondary outcomes included diastolic function, strain imaging and circulating biomarkers. Results: Four RCTs were included, of those three were conducted during anthracycline and one during trastuzumab, involving 161 patients. All trials provided absolute change in LVEF (%) after a short to medium-term of treatment exposure (≤6 months). Pooled data revealed no differences in LVEF in the exercise group versus control [mean difference (MD): 2.07%; 95% CI: −0.17 to 4.34]. Similar results were observed by pooling data from the three RCTs conducted during anthracycline. Data from trials that implemented interventions with ≥36 exercise sessions (n = 3) showed a significant effect in preventing LVEF decline favoring the exercise (MD: 3.25%; 95% CI: 1.20 to 5.31). No significant changes were observed on secondary outcomes. Conclusions: exercise appears to have a beneficial effect in mitigating LVEF decline and this effect was significant for interventions with ≥36 exercise sessions.

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